Beta-amyloid (Abeta) toxicity has been postulated to initiate synaptic loss and subsequent neuronal degeneration seen in Alzheimer's disease (AD). We previously demonstrated that beta-asarone improves cognitive function by suppressing neuronal apoptosis in vivo. In this study, we assessed the neuroprotective effects of beta-asarone against the toxicity of Abeta in relation to the mitochondria-mediated cell death process, and to elucidated the role of the ASK1/MKK7/JNK and mitochondrial pathways in beta-asarone-induced neuroprotection in SH-SY5Y cells. Our results show that beta-asarone afforded protection against Abeta-induced toxicity by inhibiting apoptosis in SH-SY5Y cells. This result was also confirmed by caspase-9 and caspase-3 activity assays. Expression of p-ASK1, p-MKK7, p-JNK, Bax, Bad, and cytochrome c release decreased after pretreatment with beta-asarone in SH-SY5Y cells exposed to A1-42. Interestingly, these effects of beta-asarone against Abeta1-42 insult were enhanced by ASK1 siRNA. These findings suggest that beta-asarone prevents Abeta1-42-induced neurotoxicity through attenuating neuronal apoptosis, and might be a potential preventive or therapeutic agent for AD.
Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/toxicity , Anisoles/pharmacology , Apoptosis/drug effects , MAP Kinase Kinase Kinase 5/physiology , Neuroprotective Agents , Allylbenzene Derivatives , Annexin A5 , Blotting, Western , Cell Death , Cell Line , Cell Survival , Flow Cytometry , Fluorescein-5-isothiocyanate , Humans , MAP Kinase Kinase Kinase 5/genetics , Mitochondria/drug effects , Neurons/drug effects , Oncogene Protein p65(gag-jun)/metabolism , RNA/biosynthesis , RNA/genetics , RNA, Small Interfering , Reverse Transcriptase Polymerase Chain Reaction , Transfection
